Nanosponge: Versatile Drug Delivery System
Nanosponges are tiny sponges with a size of about a virus (250nm – 1μm), which consist of cavities that can be filled with a wide variety of drugs.
Published on: Mar 3, 2016
Transcripts - Nanosponge: Versatile Drug Delivery System
M.Pharm – (I semister)
Under the guidance of
Dept. of Pharmaceutics
Modern college of pharmacy (for ladies), Moshi,
A BOON TO THE TARGETED DRUG DELIVERY SYSTEM
Aim & objective
What is nano sponge ?
Factors influencing the formation of nanosponges
Method of preparation
Evaluation of nanosponges
AIM : To review and study nanosponge as a novel
& targeted drug delivery system.
To discuss nanosponges with their...
Advantages & disadvantages,
Factors influencing there formation,
Method of preparation,
Nanosponges are tiny sponges with a size of about a virus
(250nm – 1μm), which consist of cavities that can be filled with
a wide variety of drugs.
The sponge acts as a three-dimensional network or scaffold, which
consist of the backbone known as long-length polyester.
It is mixed in solution with cross-linkers to form the polymer.
What Is Nano Sponge ???
Targeting the drug delivery has long been a problem for medical
researchers how to get them to the right place in the body and how
to control the release of the drug to prevent overdose.
The development of new and complex molecules called
Nanosponges has the potential to solve these problems.
Nanosponge is a novel and emerging technology which play a vital
role in targeting drug delivery in a controlled manner.
Nanosponges are a new class of materials and made of microscopic
particles with few nanometres wide cavities in which a large variety
of substances can be encapsulated.
A wide variety of drugs can be loaded into nanosponge for targeting drug
These particles are capable of carrying both lipophilic and hydrophilic
substances and of improving the solubility of poorly water soluble
Nanosponges are tiny mesh like structures is about the size of a virus
with a backbone of naturally degradable polyester.
They cross link segments of the polyester to form
a spherical shape that has many pockets / cavities where
drug can be stored.
The nanoscale materials are small enough to be effective in attaching to or passing
through cell membranes.
The polyester is biodegradable, so it breaks down gradually in the body & releases
its drug payload in a predictable fashion.
These tiny sponges can circulate around the body until they encounter the specific
target site and stick on the surface and begin to release the drug .
As compared to other nanoparticles, nanosponges are porous, non toxic and
stable at high temperatures up to 300oC.
The nanosponges are solid in nature and can be formulated as oral,
parenteral, topical or inhalational dosage forms.
For oral administration, these may be dispersed in a matrix of excipients,
diluents, lubricants which is suitable for the preparation of tablets or
For parenteral administration, these can be simply mixed with sterile water,
saline or other aqueous solutions.
For topical administration, they can be
effectively incorporated into topical
Targeted site specific drug delivery.
Can be used to mask unpleasant flavours, odour and to convert liquid
substances to solids.
Less harmful side effects (since smaller quantities of the drug have
contact with healthy tissue).
Nanosponge particles are soluble in water, so the hydrophobic drugs can
be encapsulated within the nanosponge, after mixing with a chemical
called an adjuvant reagent.
Particles can be made smaller or larger by varying the proportion of
cross-linker to polymer.
Nanosponge formulations are stable over range of ph 1 to 11.
Nanosponge formulations are stable at the temperature up to 130˚c
These formulations are compatible with most vehicles and ingredients.
These are self sterilizing as their average pore size is 0.25μm where
bacteria cannot penetrate.
These formulations are free flowing and can be cost effective
Improved stability, increased elegance and enhanced formulation
The main disadvantage of these nanosponges is their ability to include
only small molecules.
Dose dumping may take place.
May retard the release.
Materials Used For Preparation Of Nanosponges
Polymers : Hyper cross linked polystyrenes, ethyl cellulose, 2-
hydroxy proply β – cyclodextrins, poly valerolactone,
Eudragit RS 100, acrylic polymers
Cross linkers : Dichloromethane, diphenyl carbonate, acrylamido,
glutarldehyde, Carboxylic acid dianhydride ,
Type of polymer : Type of polymer used can influence the formation as well
as the performance of Nanosponges. For complexation, the cavity size of
nanosponge should be suitable to accommodate a drug molecule of particular
Type of drugs : Molecules to be complexed with nanosponges should have
certain characteristics mentioned below
1. Molecular weight between 100 – 400 Da .
2. Drug molecule consists of less than five condensed rings .
3. Solubility in water is less than 10mg/mL .
4. Melting point of the substance is below 250°C.
Factors influencing the formation of
Temperature : Increasing in the temperature decreases the stability of
the drug/nanosponge complex, may be due to a result of possible
reduction of drug/nanosponge interaction forces.
Method of preparation : The method of loading the drug into the
nanosponge can affect Drug/Nanosponge complexation.
Degree of substitution : The complexation ability of the nanosponge
may be greatly affected by type, number and position of the substituent
on the parent molecule.
• Polymer is mixed with a suitable solvent like polar aprotic solvent.
• This mixture is added to excess quantity of the cross-linker
preferably in cross-linker/polymer molar ratio of 1:4.
• Action is carried out at temperature ranging from 10°C to the reflux
temperature of the solvent, for time ranging from 1 to 48 hr
• After completion of the reaction, the solution is cooled at room
temperature and the product is added to large excess of distilled water.
5 • The recovery of the product is done by filtration under vacuum.
METHOD OF PREPARATION
1. Solvent method
Nanosponges are obtained by reacting cyclodextrin with a cross-
linker such as di isocianates, diaryl carbonates, dimethyl
carbonate, diphenyl carbonate, and carbonyl diimidazoles.
The average diameter of a Nanosponge is below 1 µm but
fractions below 500 nm can be selected.
2. Hyper Cross- Linked β- Cyclodextrins
• In this method, nanosponges can be obtained by reacting polymers
with cross-linkers in the absence of solvent and under sonication.
• The nanosponges obtained by this method will be spherical and
uniform in size.
4. Ultrasound-Assisted synthesis
Organic internal phase containing
drug & polymer in solvent is added to
External phase containing emulsifying
Than mixture is stirred at 1000-2000
rpm for 3 hrs at RT
Formed nanosponge were filtered,
washed & dried at RT
3. Emulsion Solvent Diffusion Method
nanosponges in water
and sonicate to avoid
the presence of
then centrifuge the
obtain the colloidal
supernatant and dry
the nanosponge by
disperse the excess
amount of the drug
and maintain the
constant stirring at
specific time for
or by freeze drying Nanosponges
Loading Of Drug Into Nanosponges
(undissolved) drug by
Then obtain the solid
crystals of nanosponges
Author Aim Method used Result
Formulated NS loaded
antibiotic resulted in
sustained release. Among
all batches (F5) is
considered as the best
entrapped (90.80%) NS
with greater % drug
formulation as oxygen
NS were able to
encapsulate, store &
release oxygen for
prolonged time. US
enhanced release &
permeation of oxygen. NS
is suitable carrier & act as
Author Aim Method used Result
E. K. PATEL*
delivery of calcium
SEM – roughly spherical
shape, porous in nature
& mean particle size -
400nm. zeta potential is
efficiencies – 81 – 95 %
Evaluation of the
Mechanism of Drug
A sustain release topical
DDS of econazole nitrate
developed as o NS hydro
gel offered solubilising
matrix for poorly soluble
drug. Served as a local
depot for sustain drug
Particle Size Determination : Particle size can be determined by laser
light diffractometry or Zeta seizer.
Loading Efficiency : The loading efficiency (%) of Nanosponge can be
Actual drug content
Loading Efficiency = ---------------------------------- X 100
Theoretical drug content
UV spectroscopy is used to carry out the saturated solution interaction
Increasing concentrations of nanosponge solutions (1– 80 ppm) are added
to fixed concentrations of the drug.
The samples are kept overnight for interaction and finally filtered solutions
are scanned for λmax and absorbance is measured.
Drug loading is interpreted by taking scans of the formulation in the UV
range and analyzing the shift of the absorbance maxima in the spectra
compared to pure drug.
• Saturation state interaction
Bulk volume – True volume
% Porosity (E) = ------------------------------------------ x 100
Zeta potential :
Zeta potential of any system under investigation is a measure of the
SEM and TEM :
These tools are employed to evaluate the particle shape and size
and to get morphological information related to the drug delivery
Fourier transform-infrared spectroscopy (FTIR) :
It serves as a major tool to determine the presence of functional
Porosity : Percent porosity is given by equation
Diffraction peaks for a mixture of compounds are useful in
determining chemical decomposition and complex formation.
Complex formation of the drug with nanosponges alters the
diffraction patterns and also changes the crystalline nature of
Thermo gravimetric analysis (TGA)
These studies are carried out to understand the melting point, thermo
stability and crystalline behaviour of the particle.
Powder X-ray diffraction (P-XRD)
Marking of the cylinder at a specified
Percentage of swelling = -----------------------------------------------------x 100
Initial marking before soaking
Mass of the hydro gel after 72 hrs
Percentage of water uptake = -----------------------------------------------x 100
Initial Mass of dry polymer
Swelling and water uptake
• In vitro release kinetics experiments are performed using a multi-
compartment rotating cell; an aqueous dispersion of nanosponges (1
mL) containing the drug is placed in the donor compartment, while the
receptor compartment, separated by a hydrophilic dialysis membrane,
is filled with phosphate buffer at pH 7.4 or pH 1.2.
• Each experiment is carried out for 24 h.
• At fixed times, the receptor buffer is completely withdrawn and
replaced with fresh buffer. The amount of drug in the medium is
determined by a suitable analytical method and drug release is
calculated to determine the release pattern.
Drug release kinetics
In vitro diffusion model
Gems (genetically engineered mouse models).
HT-29 cell line
MCF-7 cell line
In vivo models
Some strains of laboratory animals are susceptible to spontaneously
developing certain types of tumor.
may mimic some types of human diseases
can use to study early disease.
can use for prevention.
includes elements of progression
Variability of disease progression.
Large animal numbers needed.
Long time to develop disease.
penetrance (not all animals get disease).
Paclitaxel, camptothecin, tamoxifen, econazole nitrate, peroxidase
Trade name Market
Dexamethasone Dermal Glymesason Japan
Iodine Topical Mena-gargle Japan
Alprostadil I.V Prostavastin Europe,
Piroxicam Oral Brexin Europe
Temoxifen Oral - -
Other examples patented drugs used in nanosponge preparation
Oxygen delivery systems.
As a carrier for biocatalysts and in the delivery
and release of enzymes, proteins, vaccines and antibodies.
Harvesting of rare Cancer Marker from Blood.
Topical drug delivery system.
More effectiveness than direct injection.
The nanosponges have the ability to include either lipophilic or hydrophilic
drugs and release them in a controlled and predictable manner at the
target site. By controlling the ratio of polymer to the cross-linker the
particle size and release rate can be modulated. Nanosponges enable the
insoluble drugs and protect the active moieties from physicochemical
degradation and controlled release. Because of their small size and
spherical shape nanosponges can be developed as different dosage forms
like parenteral, aerosol, topical, tablets and capsules.
Thus, the nanosponge drug delivery system is a boon in the area of
targeted and site specific drug delivery system.
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G. Jilsha., Vidya Viswanad., Nanosponges: A Novel Approach Of Drug Delivery
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C. U. Shah, Cyclodextrin Based Nanosponges For Pharmaceutical Use: A Review;
Acta Pharm. 2013, Volume 63, Pg. No. 335-358.
S.P. Vyas, R.K. Khar. Targeted And Controlled Drug Delivery- Novel Carrier Systems.
Molecular Basis Of Targeted Drug Delivery. Cbs Publishers And Distributors. New
Delhi. 2008: Pg. No. 38- 40.
S. Subramanian, A. Singireddy., Nanosponges: A Novel Class Of Drug Delivery
System; J Pharm Pharmaceut Sci: 2012, Volume 15(1), Pg. No. 103-111.